Summary
The plasma and urine concentrations of famotidine, a new, potent H2-receptor antagonist, have been measured in 16 healthy young adults, 8 healthy elderly people and 18 patients with varying degrees of renal dysfunction after intravenous administration.
Both the plasma elimination and renal excretion of famotidine were decreased in the elderly volunteers and renal patients. The renal clearance of famotidine averaged 4.43 ml/min/kg (310 ml/min) in normal young volunteers, which exceeded the mean creatinine clearance 1.55 ml/min/kg (109 ml/min), suggesting net secretion is a significant mechanism for elimination of famotidine.
The ratio of famotidine renal clearance to creatinine clearance decreased as creatinine clearance decreased; these results suggest that the deterioration in the secretion process was much faster than that in glomerular filtration and are incompatible with the “intact nephron hypothesis”. Nevertheless, both total body clearance and renal clearance were significantly correlated with creatinine clearance.
The apparent half-life was also significantly correlated with creatinine clearance. Since famotidine is essentially free of dose-related adverse effects, dose adjustment in patients with mild renal insufficiency and in elderly people is not required; however, either a prolonged dosing interval or a decrease in daily dose during long-term therapy may be adapted for the patients with severe renal insufficiency to avoid accumulation and the potential undesirable effects.
Similar content being viewed by others
References
Doherty CC, O'Connor FA, Buchanan KD, Sloan JM, Adrill JES, McGeown MG (1977) Peptic ulcer in renal failure (abstract). Br Soc Gastroenterol 59: 62
Shepherd AMN, Stewart WK, Wormsley KG (1973) Peptic ulceration in chronic renal failure. Lancet 1: 1357–1359
Jones RH, Levin MR, Parsons V (1979) Therapeutic effect of cimetidine in patients undergoing haemodialysis. Br Med J 1: 650–652
Doherty CC, O'Connor FA, Buchanan KD, McGeown MG (1977) Cimetidine for duodenal ulceration in patients undergoing haemodialysis. Br Med J 2: 1506–1508
McCallum RW, Chremos AN, Kuljian B, Tupy-Visich MA, Huber PB (1985) MK-208, a novel histamine H2-receptor inhibitor with prolonged antisecretory effects. Dig Dis Sci 30: 1139–1144
Howard JM, Chremos AN, Collen MJ (1985) Famotidine: A new potent, long-acting histamine H2-receptor antagonist — Comparison with cimetidine and ranitidine in the treatment of Zollinger-Ellison Syndrome. Gastroenterology 88: 1026–1033
Yeh KC, Chremos AN, Lin JH, Constanzer ML, Kanovsky SM, Hucker HB, Antonello J, Vlasses P, Ryan JR, Williams RL (1987) Single-dose pharmacokinetics and bioavailability of famotidine in man — results of multi-center collaborative studies. Biopharm Drug Disp 8
Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J (1986) Effects of antacids and food on absorption of famotidine. Br J Clin Pharmacol 24: 551–553
Vincek W, Constanzer ML, Hessey GA II, Bayne WF (1985) Analytical method for the quantiation of famotidine, a new H2-receptor blocker in plasma and urine. J Chromatogr 338: 438–443
Gibaldi M, Perrier D (1982) Pharmacokinetics (2nd edn), chapter 5, Marcel Dekker, New York Basel, p 215
Bricker NS, Morrin PF, Kine SW (1960) The pathologic physiology of chronic Bright's disease; an exposition of the “intact nephron hypothesis”. Am J Med 28: 77–98
Reidenberg MM, Camacho M, Kluger J, Drayer DE (1980) Aging and renal clearance of procainamide and acetylprocainamide. Clin Pharmacol Ther 28: 732–735
Schentag JJ, Cerra FB, Calleri GM, Leising ME, French MA, Bernhard H (1981) Age, disease and cimetidine disposition in healthy subjects and chronically ill patients. Clin Pharmacol Ther 29: 737–743
Burgess E, Cutler RE, Blair AD (1980) Cimetidine pharmacokinetics in hemodialysis patients and inhibition of creatinine secretion in healthy subjects. Clin Pharmacol Ther 27: 247
Dubb JW, Stote RM, Familiar RG, Lee K, Alexander F (1978) Effect of cimetidine on renal function in man. Clin Pharmacol Ther 24: 76–83
Davis DF, Shock NW (1950) Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest 29: 496–507
Friedman SA, Raizner AE, Rosen H, Solomon NA, Sy W (1972) Functional defects in the aging kidney. Ann Int Med 76: 41–45
Drayer DE, Romankiewicz J, Lorenzo B, Reidenberg MM (1981) Age and renal clearance of cimetidine. Clin Pharmacol Ther 31: 45–50
Young CJ, Daneshmend TK, Roberts CJC (1982) Effects of cirrhosis and aging on the elimination and bioavailability of ranitidine. Gut 23: 819–823
Kawai R, Imaski H, Kawamura S (1978) Pharmacokinetics of famotidine (YM11170), a new histamine H2-receptor antagonist. Data on file. Yamanouchi, Japan
Fabre J, Balant L (1976) Renal failure, drug pharmacokinetics and drug action. Clin Pharmacokinet 1: 99–120
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lin, J.H., Chremos, A.N., Yeh, K.C. et al. Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man. Eur J Clin Pharmacol 34, 41–46 (1988). https://doi.org/10.1007/BF01061415
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01061415